The present project intends to advance the understanding of the molecular basis of the polymerization of Hb S. We intend to investigate the pregelling events, the role of non-Hb S molecules, and the supramolecular structure of the polymer. We intend to pursue the kinetics of sickling, the ligand kinetics of Hb S containing red cells and the basis of the changes in the oxygen equilibrium curve in these cells. We will continue the development of nitrogen mustards and alkylureas as antisickling agents. We will also inquire into the basis of the stimulation of the synthesis of Hb F in some pathological states, with the hope of understanding its operative control.